scholarly journals Lysosomal Membrane Permeability Stimulates Protein Aggregate Formation in Neurons of a Lysosomal Disease

2013 ◽  
Vol 33 (26) ◽  
pp. 10815-10827 ◽  
Author(s):  
M. C. Micsenyi ◽  
J. Sikora ◽  
G. Stephney ◽  
K. Dobrenis ◽  
S. U. Walkley
2014 ◽  
Vol 307 (3) ◽  
pp. F326-F336 ◽  
Author(s):  
Xiqian Lan ◽  
Aakash Jhaveri ◽  
Kang Cheng ◽  
Hongxiu Wen ◽  
Moin A. Saleem ◽  
...  

Development of higher rates of nondiabetic glomerulosclerosis (GS) in African Americans has been attributed to two coding sequence variants (G1 and G2) in the APOL1 gene. To date, the cellular function and the role of APOL1 variants (Vs) in GS are still unknown. In this study, we examined the effects of overexpressing wild-type (G0) and kidney disease risk variants (G1 and G2) of APOL1 in human podocytes using a lentivirus expression system. Interestingly, G0 inflicted podocyte injury only at a higher concentration; however, G1 and G2 promoted moderate podocyte injury at lower and higher concentrations. APOL1Vs expressing podocytes displayed diffuse distribution of both Lucifer yellow dye and cathepsin L as manifestations of enhanced lysosomal membrane permeability (LMP). Chloroquine attenuated the APOL1Vs-induced increase in podocyte injury, consistent with targeting lysosomes. The chloride channel blocker DIDS prevented APOL1Vs- induced injury, indicating a role for chloride influx in osmotic swelling of lysosomes. Direct exposure of noninfected podocytes with conditioned media from G1- and G2-expressing podocytes also induced injury, suggesting a contributory role of the secreted component of G1 and G2 as well. Adverse host factors (AHFs) such as hydrogen peroxide, hypoxia, TNF-α, and puromycin aminonucleoside augmented APOL1- and APOL1Vs-induced podocyte injury, while the effect of human immunodeficiency virus (HIV) on podocyte injury was overwhelming under conditions of APOLVs expression. We conclude that G0 and G1 and G2 APOL1 variants have the potential to induce podocyte injury in a manner which is further augmented by AHFs, with HIV infection being especially prominent.


2020 ◽  
Vol 8 (3) ◽  
pp. 343 ◽  
Author(s):  
Xun Wang ◽  
Cody G. Cole ◽  
Cory D. DuPai ◽  
Bryan W. Davies

Desiccation tolerance has been implicated as an important characteristic that potentiates the spread of the bacterial pathogen Acinetobacter baumannii on dry surfaces. Here we explore several factors influencing desiccation survival of A. baumannii. At the macroscale level, we find that desiccation tolerance is influenced by cell density and growth phase. A transcriptome analysis indicates that desiccation represents a unique state for A. baumannii compared to commonly studied growth phases and strongly influences pathways responsible for proteostasis. Remarkably, we find that an increase in total cellular protein aggregates, which is often considered deleterious, correlates positively with the ability of A. baumannii to survive desiccation. We show that inducing protein aggregate formation prior to desiccation increases survival and, importantly, that proteins incorporated into cellular aggregates can retain activity. Our results suggest that protein aggregates may promote desiccation tolerance in A. baumannii through preserving and protecting proteins from damage during desiccation until rehydration occurs.


2009 ◽  
Vol 115 (4) ◽  
pp. 1479-1485 ◽  
Author(s):  
Kelly L. Flett ◽  
Milena Corredig

2022 ◽  
Vol 100 (S267) ◽  
Author(s):  
Ali Koskela ◽  
Johanna Ruuth ◽  
Szabolcs Felszeghy ◽  
Kai Kaarniranta

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi78-vi78
Author(s):  
Pim French ◽  
Ya Gao ◽  
Maurice de Wit ◽  
Darlene Mercieca ◽  
Iris de Heer ◽  
...  

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